Discovery of 4鈥?azido-2鈥?deoxy-2鈥?C-methyl cytidine and prodrugs thereof: A potent inhibitor of Hepatitis C virus replication

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• 作者：Magnus Nilsson^a ; ^{magnus.k.nilsson@telia.com} ; Genadiy Kalayanov^a ; Anna Winqvist^a ; Pedro Pinho^a ; Christian Sund^a ; Xiao-Xiong Zhou^a ; Horst Wä ; hling^a ; Anna-Karin Belfrage^a ; Michael Pelcman^a ; Tatiana Agback^a ; Kurt Benckestock^a ; Kristina Wikströ ; m^a ; Mirva Boothee^a ; Anneli Lindqvist^a ; Christina Rydeg&aring ; rd^a ; Tim H.M. Jonckers^b ; Koen Vandyck^b ; Pierre Raboisson^b ; Tse-I Lin^b ; Sophie Lachau-Durand^b ; Herman de Kock^b ; David B. Smith^c ; Joseph A. Martin^c ; Klaus Klumpp^c ; Kenneth Simmen^b ; Lotta Vrang^a ; Ylva Terelius^a ; Bertil Samuelsson^a ; &Aring ; sa Rosenquist^a ; Nils Gunnar Johansson^a
• 关键词：Hepatitis C virus ; NS5B polymerase ; Antivirals ; Nucleoside ; Prodrug ; Phosphoramidate
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2012
• 期刊代码：10_0960894x
• 类别：ch
• 出版时间：1 May, 2012
• 卷：22
• 期：9
• 页码：3265-3268
• 文件大小：325 K

摘要

4鈥?Azido-2鈥?deoxy-2鈥?methylcytidine (14) is a potent nucleoside inhibitor of the HCV NS5B RNA-dependent RNA polymerase, displaying an EC₅₀ value of 1.2 渭M and showing moderate in vivo bioavailability in rat (F = 14%). Here we describe the synthesis and biological evaluation of 4鈥?azido-2鈥?deoxy-2鈥?methylcytidine and prodrug derivatives thereof.